Isoflurane Anesthesia Attenuates Endothelium-dependent Pulmonary Vasorelaxation by Inhibiting the Synergistic Interaction between Nitric Oxide and Prostacyclin

Background: Endothelium-derived nitric oxide causes vasodilation in part by increasing the dilator activity of other endothelium-derived mediators, including prostacyclin and a K sup +ATP channel-dependent hyperpolarizing factor. Although previous studies have proposed that isoflurane (ISO) depresses endothelium-dependent vasorelaxation by inhibiting endothelium-derived nitric oxide activity, the effects of ISO on the interactions among endothelium-derived dilators have not been characterized. The aim of this study was to determine the mechanisms underlying the inhibitory effect of ISO on endothelium-dependent relaxation in canine pulmonary arteries. Specifically, the goal was to assess the effects of ISO on the individual actions and on the synergistic interactions of these endothelium-derived mediators.

Methods: Canine pulmonary arterial rings were suspended for isometric tension recording. The effects of 1 minimum alveolar concentration ISO (0.4 mM) on vasorelaxation responses to bradykinin, A23187, acetylcholine, cromakalim, and SIN-1 were assessed in phenylephrine-precontracted rings with and without pretreatment with a nitric oxide synthase inhibitor (N sup omega -nitro-L-arginine methyl ester; L-NAME), a cyclooxygenase inhibitor (indomethacin), or a K sup +ATP, channel inhibitor (glybenclamide).

Results: Isofluane attenuated pulmonary vasorelaxation induced by bradykinin, A23187, and cromakalim but had no effect on relaxation induced by acetylcholine or SIN-1. Neither the nitric oxide-mediated nor the prostacyclin-mediated components of relaxation induced by bradykinin and A23187 were altered by ISO. However, ISO abolished the K sup +ATP -mediated component of relaxation and the K sup +ATP -dependent synergistic interaction between nitric oxide and prostacyclin.     

Evaluation of an Algorithm To Identify Women with Carcinoma of the Breast

Although claims data are increasingly being used to measure and manage the cost and quality of health care, few studies have evaluated algorithms developed for such analyses. Therefore, the present study was performed to evaluate prospectively a previously published algorithm used to identify women with the new diagnosis of carcinoma of the breast. This algorithm had been developed from the patterns of claims that suggested common clinical presentations of carcinoma of the breast. In the present study, this algorithm was used to identify 177 potential cases of women with newly diagnosed carcinoma of the breast from the claims database of a large health maintenance organization (HMO). The algorithm's positive predictive value for cases identified in the present study was 83% (147/177). To attempt to improve upon the positive predictive value, multiple modifications of the algorithm were performed. The previously defined best modification of the initial algorithm yielded a positive predictive value of 84% (147/174) in the present study with the loss of none of the true positive cases. These results demonstrate that logic-based algorithms can be used as a valid and efficient method of identifying large numbers of new breast cancer cases from claims data. This algorithm provides a powerful tool to perform health care analysis and research for women with newly diagnosed carcinoma of the breast.     

RESULTS OF OPEN CARPAL TUNNEL RELEASE: A COMPREHENSIVE,RETROSPECTIVE STUDY OF 188 HANDS

Background : Many recent reports of the results of decompression of the median nerve in the carpal tunnel have concentrated on only one aspect of recovery (numbness, grip etc.), and there are no reports of a comprehensive study of outcome. The aim of the present study was to review comprehensively the results of the direct visualization method of decompression of the carpal tunnel and to compare them with the published results of endoscopic release. Methods : Patients' perceptions of the severity of pain, numbness and paraesthesiae due to carpal tunnel syndrome (CTS), before and after open carpal tunnel release (CTR) in 188 hands were reviewed retrospectively at a minimum time of follow-up of 18 months. Motor and sensory testing, provocation testing and measurement of scar tenderness in 135 hands were performed at a clinical review. Results : Subjective results showed that 70% experienced a reduction in the severity of pain after CTR, 78% of hands experienced a reduction in the severity of paraesthesiae and 77% experienced a reduction in the severity of numbness. A total of 49% had improvements in all three symptoms after CTR. At the clinical review, sensory testing revealed that 59% of hands had normal or slightly diminished light touch, 35% had normal static two-point discrimination and 61% had normal dynamic two-point discrimination. Results for Tinel's test, Phalen's test and pressure provocation testing were positive in 10% of hands. There was no scar tenderness in 38%, no persisting thenar atrophy in 90%. Normal grip strength was found in 93% and 91% had normal pinch strength. Conclusions : It was concluded that open carpal tunnel release remains a safe and reliable treatment for carpal tunnel syndrome. The very low incidence of serious complications from the open technique of CTR, when compared with endoscopic CTR as published by different authors in the literature, and the comparable clinical results, appears to make the open technique a safer and preferable option. However, a properly controlled trial of both techniques is necessary to compare them.     

Isolation of a peptide that inhibits the posttranslational arginylation of proteins in rat brain

All eukaryotic cells contain enzymes that are able to catalyze the transfer of Arg from tRNA to the N-terminus of naturally short lived or damaged cytosolic proteins. For certain test proteins, it has been shown that the addition of Arg to the N-terminus leads to their degradation via the ubiquitin proteolytic pathway. The mechanisms used by cells for identifying proteins for arginylation and regulating arginylation are not known. The present study reports the isolation of a peptide from rat brain that is able to inhibit the arginylation of proteins in brain extracts. We suggest that this peptide is the physiological regulator of arginylation in rat brain.     

The effects of phorbol esters with different biological activities on protein kinase C

The sapintoxins are a series of naturally occurring fluorescent phorbol esters with a range of selective biological activities (e.g. pro-inflammatory but non-tumour promoting). Their ability to activate protein kinase C (PKC) in vitro has been studied. Both tumour promoting and non-promoting phorbol derivatives activate the enzyme in vitro at low concentrations. 12-deoxyphorbol-13-phenylacetate-20 acetate (DOPPA) acts as a partial agonist in the activation of protein kinase C. Structurally distinct phorbol esters may therefore preferentially activate different forms of protein kinase C. α-sapinine, a biologically inactive compound, binds to protein kinase C without stimulating the enzyme and prevents subsequent activation by phorbol esters such as 12-O-tetradecanoyl phorbol-13-acetate (TPA).     

Prediction of global outcome with acute neuropsychological testing following closed-head injury.

Delaying assessment until emergence from post-traumatic amnesia increases completion rates, but this practice causes variable time delays from the date of injury to testing, which can complicate the interpretation of research findings. In the current study, the performance of 105 head injury survivors on simple tests of language comprehension and attention was used to predict global outcome. It was hypothesized that 1 month performance on these measures would aid in the prediction of Disability Rating Scale (DRS) and Glasgow Outcome Scale (GOS) scores collected at 6 months post injury. Only raw scores on the modified Test of Complex Ideational Material accounted for a significant amount of the variance in DRS scores (4.4%) above that accounted for by age, education, Glasgow Coma Scale score, and pupil response. However, testability at 1 month post injury on all four tests consistently accounted for a larger portion of the variance in DRS scores (10.1-13.2%) and significantly improved prediction of GOS scores. Galveston Orientation and Amnesia Test scores collected at 1 month post injury accounted for substantially less variance in DRS scores (7.7-8.4%). Neuropsychological data, including the testability of patients, collected uniformly at 1 month following injury can contribute to the prediction of global outcome.